Effects of Histone H3 and H4 Core Domain Mutations on DNA Replication
Beam, Nicholas W.
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Chromatin refers to the complex of DNA and proteins, primarily histones, which exists in the nucleus. Its structure is responsible for regulation of a number of processes such as DNA replication and transcription. Histones are vital chromatin proteins which are significantly involved in the structure of chromatin. They are octameric complexes made up of pairs of four different subunits, H2A, H2B, H3 and H4, around which DNA wraps. Modification of residues on the amino tail of these subunits is quite well understood, however the importance of residues in the core folding domain of these subunits is an area of histones which has not been heavily studied. This study sought to use a plasmid shuffling system to create yeast mutant strains in order to identify mutations of interest in histones H3 and H4, specifically those related to DNA replication. These strains were spotted at different temperatures in order to assess their growth phenotype relative to wild-type histone H3 and H4 subunits. Several residues of interest were identified. Two residues, H3 K122 and H4 K91, seemed to indicate playin a more direct role in regulating DNA replication. Additionally H4 V43, H4 R45 and H4 S47 were identified as important sites for fully functional histones, but this was not directly tied to DNA replication. These identified residues provide a starting point for future research into the role and mechanism of the histone core domain in regulating DNA replication.